麻豆传媒

The spleen tyrosine kinase inhibitor fostamatinib (Tavalisse) did not improve outcomes in adults hospitalized with COVID-19 and hypoxemia, according to a phase III trial published in .

In this exclusive 麻豆传媒 video, Sean P. Collins, MD, MSc, of Vanderbilt University Medical Center in Nashville, Tennessee, discusses the implications of the trial findings, highlighting how differences in patient populations and the evolving nature of COVID-19 might have influenced the results.

Following is a transcript of his remarks:

So we conducted a randomized placebo-controlled trial of fostamatinib in in-patients hospitalized with COVID-19 and new hypoxemia. So somebody who wasn't on oxygen as an outpatient who developed an oxygen requirement in the hospital, or somebody who was on oxygen as an outpatient but had an increased requirement in the hospital. That was largely the group that we enrolled.

And we designed our trial with a lot of characteristics that were consistent with the two prior trials, the phase II and phase III trial that had shown fostamatinib may have efficacy in patients with COVID-19. So a lot of design characteristics were very similar amongst our three studies.

What we found, our primary outcome was oxygen-free days, and this was a combination of surviving COVID-19 and no longer requiring oxygen at this new level. So basically leaving the hospital and being back off oxygen and back to your activities of daily living.

We chose this because it was important to investigators but also important to patients. We had discussed with several different patients, patient advocate groups, the importance of being liberated from oxygen, so not having to bring oxygen around with you for your activities of daily living.

And so the results of the trial suggested that fostamatinib did not improve oxygen-free days. So this combination of mortality and oxygen requirement in our patient populations. Which was a bit surprising obviously given that the first two studies suggested that fostamatinib helped improve oxygen requirements and especially in those patients who were severe, so were on very high levels of oxygen, it looked like it may have helped them disproportionately to patients who were on lower levels of oxygen.

And I think what we really learned, it was the same medication studied in a similar patient population characteristics-wise, what we really learned is that COVID was just a much different disease at the end of the pandemic compared to the beginning. And so differences in vaccination. Our patients were much older than patients in the two prior trials. Our patients had a lot of comorbidities, including underlying lung disease, which just wasn't present -- At the beginning of the pandemic, it was young, healthy people who were getting horribly sick. And at the end of the pandemic, it was patients who were already vaccinated having breakthrough infections likely related to their underlying comorbidities, including lung disease.

So while it was surprising, I think even more important will be our mechanistic substudy of this, understanding at baseline, how much of this lung injury or lung disease was due to COVID infection and inflammation versus worsening of a person with chronic underlying lung disease who didn't have a large component of COVID. That maybe just had tipped them over the edge. And I think that will be as informative as the results of our phase III trial, quite honestly.

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